Studies of the signal transduction mediated by IL 1 receptors and post receptor molecular events have established that IL I rapidly phosphorylates 65 and 74 kDa cytosolic proteins at serine residues in human peripheral blood mononuclear cells (PBMC) through activation of an unidentified protein kinase which is distinct from protein kinase C, protein kinase A, or casein kinase. The phospho 65 kDa protein has been purified, molecularly cloned, and identified to be 1-plastin. Tumor necrosis factor and PMA which have many overlapping biological activities with IL 1 also activate the same serine kinase and phosphorylate the identical cytosolic proteins. The IL I/TNF/PMA responsive promotor region of IL 8 gene was localized to the region -94 to -71 bp, which consists of C/EBP and NFkB-like factor binding elements. The nuclear factors bound to these elements may also be similarly phosphorylated and activated by IL I/TNF/PMA activated serine kinase. The identification of novel IL 1/TNF inducible cytokines has enabled us to purify and molecularly clone the cDNAs of two novel leukocyte chemotactic and activating factors, i.e. neutrophil/lymphocyte chemotactic and activation factor (newly named interleukin 8), and monocyte chemotactic and activating factor (termed MCAF). Biological, biochemical and physiochemical properties of these molecules have been determined and the receptors for these molecules have been partially characterized.